87 research outputs found
What Do We Know about Mediators of Inflammation in the Horse?
Equine inflammatory airway disease (IAD) and recurrent airway obstruction
(RAO) represent a spectrum of chronic inflammatory disease of the airways in
horses resembling human asthma in many aspects. Therefore, both are now
described as severity grades of equine asthma. Increasing evidence in horses
and humans suggests that local pulmonary inflammation is influenced by
systemic inflammatory processes and the other way around. Inflammation,
coagulation, and fibrinolysis as well as extracellular remodeling show close
interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is
commonly used to evaluate the severity of local inflammation in the lung.
Other mediators of inflammation, like interleukins involved in the chemotaxis
of neutrophils, have been studied. Chronic obstructive pneumopathies lead to
remodeling of bronchial walls and lung parenchyma, ultimately causing
fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important
proteolytic enzymes during remodeling in human medicine and increasing
evidence exists for the horse as well. A systemic involvement has been shown
for severe equine asthma by increased acute phase proteins like serum amyloid
A and haptoglobin in peripheral blood during exacerbation. Studies focusing on
these and further possible inflammatory markers for chronic respiratory
disease in the horse are discussed in this review of the literature
Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma
Objectives. Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-ODN) normalizes clinical and cytologic parameters in severe equine asthma. We hypothesized that CpG-ODN inhalation also reduces the misbalance of elastinolytic activity in asthmatic horses. Methods. Twenty asthmatic horses diagnosed by clinical examinations using a scoring system were included. All horses inhaled CpG-ODNs for 14 days in 2-day intervals. Matrix metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) concentrations were measured in tracheal aspirates using equine sandwich ELISAs before and 2 and 6 weeks after CpG-ODN inhalation. Results. MMP and TIMP concentrations correlated with the results of clinical scoring in all stages of equine asthma. Inhalation therapy led to significant reductions in clinical scores. MMP-2, MMP-9, and TIMP-2 concentrations were significantly reduced immediately, and all MMP and TIMP concentrations 6 weeks after therapy. Discussion. In equine asthma, overexpression of MMPs contributes to pathological tissue destruction, while TIMPs counteract MMPs with overexpression leading to fibrosis formation. The results of this study show that CpG-ODN inhalation may be an effective therapy to address a misbalance in equine asthma. Conclusions. Misbalance of elastinolytic activity seems to improve by CpG-ODN inhalation for at least 6 weeks posttherapy, which may reduce the remodeling of the extracellular matrix. Further studies should evaluate this effect in comparison to glucocorticoid inhalation therapy. Significance. CpG-ODN inhalation may be an effective therapy in the prevention of pulmonary fibrosis formation in equine asthma
Pharyngeal diameter in various head and neck positions during exercise in sport horses
Background In equine athletes, dynamic stenotic disorders of the upper airways
are often the cause for abnormal respiratory noises and/or poor performance.
There are hypotheses, that head and neck flexion may influence the morphology
and function of the upper airway and thus could even induce or deteriorate
disorders of the upper respiratory tract. Especially the pharynx, without
osseous or cartilaginous support is prone to changes in pressure and airflow
during exercise. The objective of this study was to develop a method for
measuring the pharyngeal diameter in horses during exercise, in order to
analyse whether a change of head-neck position may have an impact on the
pharyngeal diameter. Results Under the assumption that the width of the
epiglottis remains constant in healthy horses, the newly developed method for
calculating the pharyngeal diameter in horses during exercise is unsusceptible
against changes of the viewing-angle and distance between the endoscope and
the structures, which are to be assessed. The quotient of the width of the
epiglottis and the perpendicular from a fixed point on the dorsal pharynx to
the epiglottis could be used to determine the pharyngeal diameter. The
percentage change of this quotient (pharynx-epiglottis-ratio; PE-ratio) in the
unrestrained head-neck position against the reference position was
significantly larger than that of any other combination of the head-neck
positions investigated. A relation between the percentage change in PE-ratio
and the degree of head and neck flexion could not be confirmed. Conclusions It
could be shown, that the pharyngeal diameter is reduced through the contact
position implemented by the rider in comparison to the unrestrained head and
neck position. An alteration of the pharyngeal diameter depending on the
degree of head and neck flexion (represented by ground and withers angle)
could not be confirmed
Procalcitonin as a biomarker in equine chronic pneumopathies
Background Procalcitonin (PCT), a precursor protein of the hormone calcitonin,
is a sensitive inflammatory marker in human medicine, which is primarily used
for diagnosis of bacterial sepsis, but is also useful in diagnosis of
exacerbation of asthma and COPD. In this study, PCT was evaluated as a
potential biomarker for different chronic pneumopathies in the horse using an
equine specific ELISA in comparison to established clinical markers and
different interleukins. Sixty-four horses were classified as free of
respiratory disease, recurrent airway obstruction (RAO), inflammatory airway
disease (IAD) or chronic interstitial pneumopathy (CIP) using a scoring
system. PCT concentrations were measured in plasma (n = 17) and in the cell-
free supernatant of bronchoalveolar lavage (n = 64). PCT concentrations were
correlated to interleukins IL-1Ăź and IL-6 in BALF, clinical findings and BALF
cytology. Results The median PCT concentrations in plasma were increased in
respiratory disease (174.46 ng/ml, n = 7) compared to controls (13.94 ng/ml, n
= 10, P = 0.05) and correlated to PCT in BALF supernatant (rs = 0.48).
Compared to controls (5.49 ng/ml, n = 15), median PCT concentrations in BALF
supernatant correlated to the overall clinical score (rs = 0.32, P = 0.007)
and were significantly increased in RAO (13.40 ng/ml, n = 21) and IAD (16.89
ng/ml, n = 16), while no differences were found for CIP (12.02 ng/ml, n = 12).
No significant increases were found for IL-1 and IL-6 between controls and
respiratory disease in general as well as different disease groups.
Conclusions Although some correlations were found between PCT in plasma, BALF
supernatant and clinical scores, PCT in BALF does not seem to be a superior
marker compared to established clinical markers. PCT in plasma seems to be
more promising and a greater number of samples should be evaluated in further
studies
is equine disease comparable to what we know in humans?
This review summarizes similarities and differences between the metabolic
syndromes in humans and equines, concerning the anatomy, symptoms, and
pathophysiological mechanisms. In particular, it discusses the structure and
distribution of adipose tissue and its specific metabolic pathways.
Furthermore, this article provides insights and focuses on issues concerning
laminitis in horses and cardiovascular diseases in humans, as well as their
overlap
Procalcitonin - A Useful Biomarker for Pneumonia Associated with Rhodococcus equi?
Background: Procalcitonin, a precursor protein of the hormone calcitonin, is a
sensitive marker for sepsis in human medicine, which is used for diagnosis of
bacterial pneumonia in adults and neonates to initiate antibiotic therapy.
Objectives: In this study, procalcitonin was evaluated as a potential
biomarker for Rhodococcus equi associated pneumonia. Methods: In four foals
procalcitonin was measured at four time-points (day 0 before antibiotic
therapy, day 1, 3 and 5/6 during therapy) in plasma using an equine specific
ELISA. Inclusion criteria for the study were a positive sepsis score,
ultrasonographic evidence of pulmonary abscesses in addition >8 cm, a positive
microbiology out of tracheobronchial secretion and positive response to
antibiotic treatment (azithromycin 10 mg/kg BDW 24q PO and rifampicin 10 mg/kg
BDW 12q PO) within a weak including improvement of clinical status and
reduction of ultrasonographic score <8 cm. Results: Procalcitonin
concentrations remained below the working range of the ELISA (25 - 1000 ng/ml)
in all but one sample. Conclusions: Procalcitonin cannot be regarded a useful
biomarker in pneumonia associated with Rhodococcus equi
Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?
Are pulmonary hemostasis and fibrinolysis out of balance in equine chronic pneumopathies?
Clinical examination, bronchoalveolar lavage fluid (BALF) cytology, acute-
phase protein, and pulmonary hemostasis and fibrinolysis marker (fibrinogen,
serum amyloid A [SAA], and D-dimer) results were compared between control and
respiratory disease-affected horses. Using a clinical scoring system, horses
(n = 58) were classified as respiratory disease-free (Controls, n = 15) or
with recurrent airway obstruction (RAO; n = 18), inflammatory airway disease
(n = 14) or chronic interstitial pneumopathy (n = 11). There were no
significant differences in fibrinogen concentrations among groups, but there
was a trend toward a lower value in controls (median 0.0024 g/L) than in
horses with chronic pneumopathies (median 0.0052 g/L), in particular, those
with RAO (median 0.0062 g/L). Fibrinogen concentration was positively
correlated with percentage of neutrophils in BALF (rs = 0.377, p = 0.004). SAA
concentrations were low; 65.5% of samples were below the detection limit.
D-dimer concentrations were also low and quantifiable concentrations were only
obtained after ultrafiltration and only in RAO (median 0.1 mg/L). In
conclusion, there was limited evidence of increased coagulatory activity in
chronic pneumopathies, apart from RAO. It is uncertain whether fibrinogen and
D-dimer concentrations increased due to their role as acute-phase proteins or
as a misbalance of coagulation and fibrinolysis
Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse
In chronic respiratory disease, matrix metalloproteinases (MMPs) contribute to
pathological tissue destruction when expressed in excess, while tissue
inhibitors of metalloproteinases (TIMPs) counteract MMPs with overexpression
leading to fibrosis formation. They may be out of balance in equine
pneumopathies and serve as biomarkers of pulmonary inflammation. We
hypothesized that MMPs and TIMPs correlate to clinical findings and
bronchoalveolar lavage fluid cytology in different equine chronic
pneumopathies. Using a scoring system, 61 horses were classified controls as
free of respiratory disease (n=15), recurrent airway obstruction (RAO, n=17),
inflammatory airway disease (IAD, n=18), or chronic interstitial pneumopathy
(CIP, n=11). Zymography and equine MMP and TIMP assays were used to detect
MMP-2, MMP-8, MMP-9 as well as TIMP-1, and TIMP-2 in BALF supernatant. MMP-2,
TIMP-1, and TIMP-2 concentrations were significantly increased in RAO and IAD
compared to controls. MMP-9 concentration and MMP-8 activity evaluated by
fluorimetry were significantly increased in RAO, IAD, and CIP. These results
were confirmed by zymography for MMP-2 and MMP-9 activity in 52 horses. In
conclusion, MMPs and TIMPs correlate well with clinical and cytologic
findings. These findings support the usefulness of MMPs, TIMPs, and their
ratios to evaluate the severity of respiratory disease and may help to
identify subclinical cases
Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction
Background Overexpression of matrix-metalloproteinases (MMPs) has been shown
to lead to tissue damage in equine recurrent airway obstruction (RAO), as a
misbalance with their natural inhibitors, the tissue inhibitors of
metalloproteinases (TIMPs), occurs. This favors irreversible pulmonary
fibrosis formation. Increased levels of MMPs, TIMPs or altered ratios between
them can be used as biomarkers of respiratory disease. We hypothesized that
levels of MMPs, TIMPs and their ratios correlate with improvement in clinical
findings and bronchoalveolar lavage fluid (BALF) cytology after 10 days of
inhalative glucocorticoid therapy and environmental dust reduction (EDR) and
may be used to monitor treatment success. Ten horses with a history of RAO
participated in a prospective clinical study. Clinical and cytological scoring
was performed before and after inhalative therapy using budesonide (1500 ÎĽg
BID over 10 days) and EDR (bedding of wood shavings and wet hay as roughage).
Gelatin zymography was performed for qualitative and semi-quantitative
evaluation of MMP-2 and MMP-9 in BALF supernatant, while fluorimetry was used
to evaluate MMP-8 activity. Additionally, specific equine ELISA assays were
used for quantitative assessment of MMP-2, MMP-9, TIMP-1 and TIMP-2. Results A
significant reduction in the total and several single parameters of the
clinical score were found after 10 days of inhalative therapy and EDR. The
concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 (ELISA) as well as their
activities (MMP-2 and MMP-9 zymography and MMP-8 fluorimetry) were
significantly decreased after therapy. Significant improvements in
MMP-8/TIMP-1 and MMP-8/TIMP-2 ratios were also found, differences between
other ratios before and after therapy were insignificant. Conclusions
Metalloproteinases and their inhibitors, in particular MMP-9 and TIMP-2, are
valuable markers for clinical improvement in RAO
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